J Cancer 2017; 8(4):691-703. doi:10.7150/jca.17210

Research Paper

Predictive Value of UGT1A1*28 Polymorphism In Irinotecan-based Chemotherapy

Xing-Han Liu1*, Jun Lu2*, Wei Duan3, Zhi-Ming Dai4, Meng Wang1, Shuai Lin1, Peng-Tao Yang1, Tian Tian1, Kang Liu1, Yu-Yao Zhu1, Yi Zheng1, Qian-Wen Sheng1, Zhi-Jun Dai1✉

1. Department of Oncology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China;
2. Clinical Research Center, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China;
3. School of Medicine, Deakin University, Waurn Ponds, Victoria, Australia;
4. Department of Anesthesia, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
* co-first authors

Abstract

The UGT1A1*28 polymorphism was suggested to be significantly connected with irinotecan-induced toxicity and response to chemotherapy. However, the results of previous studies are controversial. Hence we carried out a meta-analysis to investigate the effect of UGT1A1*28 polymorphism on severe diarrhea, neutropenia, and response of patients who had undergone irinotecan-based chemotherapy. The PubMed, Web of Science, Wanfang, and CNKI databases were searched for clinical trials assessing the association of UGT1A1*28 polymorphism with severe diarrhea, neutropenia, and response to irinotecan-based chemotherapy. The combined odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the relationship under a fixed- or random-effects model. Fifty-eight studies including 6087 patients with cancer were included. Our results showed that patients carrying the TA6/7 and TA7/7 genotypes had a greater prevalence of diarrhea and neutropenia than those with the TA6/6 genotype (TA6/7+TA7/7 vs. TA6/6: diarrhea, OR = 2.18, 95%CI = 1.68-2.83; neutropenia, OR = 2.15, 95%CI = 1.71-2.70), particularly patients with metastatic colorectal cancer. Stratified analysis showed that Asians with the TA6/7 and TA7/7 genotypes were more likely to have diarrhea and neutropenia, and Caucasians with the TA6/7 and TA7/7 genotypes were more likely to have neutropenia than other groups. However, patients with the TA6/7+TA7/7 genotypes showed a higher response than patients with TA6/6 genotype (OR = 1.20, 95%CI = 1.07-1.34), particularly Caucasians (OR = 1.23, 95%CI = 1.06-1.42) and patients with metastatic colorectal cancer (OR = 1.24, 95%CI = 1.05-1.48). Our data showed that the UGT1A1*28 polymorphism had a significant relationship with toxicity and response to irinotecan-based chemotherapy. This polymorphism may be useful as a monitoring index for cancer patients receiving irinotecan-based chemotherapy.

Keywords: UGT1A1*28, diarrhea, neutropenia, response.

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How to cite this article:
Liu XH, Lu J, Duan W, Dai ZM, Wang M, Lin S, Yang PT, Tian T, Liu K, Zhu YY, Zheng Y, Sheng QW, Dai ZJ. Predictive Value of UGT1A1*28 Polymorphism In Irinotecan-based Chemotherapy. J Cancer 2017; 8(4):691-703. doi:10.7150/jca.17210. Available from http://www.jcancer.org/v08p0691.htm